The output of the inferior olive, described as climbing fibers in the cerebellar cortex, has been implicated as playing a critical role in "cerebellar learning". Changes in olivary output result in significant alterations in the firing pattern of Purkinje cells in the cerebellar cortex. The nature of olivary output is modified by multiple afferent systems and by local inhibitory circuits which have been postulated to play a role in regulating the synchronous firing of olivary neurons. Further, it has been shown that serotonin (5HT) may be the neurochemical mediator of local inhibitory circuits. However, in addition to 5HT at east two other putative inhibitory neurotransmitters have been identified-enkephalin (ENK) and gamma aminobutyric acid (GABA). The specific aims of this proposal are: 1) to compare the distribution of 5HT, ENK and GABA in the inferior oolivary complex of the rat using the indirect peroxidase antiperoxidase (PAP) technique of Sternberger (13); 2) to identify the cell bodies of origin for these putative neurotransmitters to the inferior olivary complex using a double labeling technique which combines retrograde transport of horseradish peroxidase with the PAP technique in order to identify the putative neurotransmitters used by reticulo-olivary neurons; and 3) to determine the physiological and morphological characteristics of serotoninergic neurons in the medullary reticular formation, especially those which participate in the local circuitry of the inferior olivary complex, using a double labelling technique which combines intracellular recording and staining of individual neurons with fluorescent immunohistochemical techniques (30-34). These neurons will be analyzed at the light and electron microscopic level in order to determine the nature of their interaction in the olivary coplex. In summary, the manner in which information is processed within a nucleus has a direct relationship on its output. In the olivo-cerebellar circuit, suble changes in climbing fiber input may result in significant alterations in Purkinje cell responsiveness and ultimately in cerebellar output. Thus, data obtained in this project should extend our knowledge of the role local circuits in the inferior olivary complex play in cerebellar mediated movements.